Severalformsofpost-translationalmodificationregulateproteinactivities.Recently,proteinmethylationbyCARM1(coactivator-associatedargininemethyltransferase1)hasbeenobservedtoplayakeyroleintranscriptionalregulation.CARM1associateswiththep160classoftranscriptionalcoactivatorsinvolvedingeneactivationbysteroidhormonefamilyreceptors.CARM1alsointeractswithCBP/p300transcriptionalcoactivatorsinvolvedingeneactivationbyalargevarietyoftranscriptionfactors,includingsteroidhormonereceptorsandCEBP.OnetargetofCARM1isthecorehistonesH3andH4,whicharealsotargetsofthehistoneacetylaseactivityofCBP/p300coactivators.RecruitmentofCARM1tothepromoterregionbybindingtocoactivatorsincreaseshistonemethylationandmakespromoterregionsmoreaccessIBLefortranscription.AnothertargetofCARM1methylationisacoactivatoritinteractswith,CBP.MethylationofCBPbyCARM1blocksCBPfromactingasacoactivatorforCREBandredirectsthelimitedCBPpoolinthecelltobeavailableforsteroidhormonereceptors.Otherformsofpost-translationalproteinmodificationsuchasphosphorylationarereversibleinnature,butasofyetaproteindemethylaseisnotknown.ThemethylationactivityofCARM1modulatestheactivityofspecifictranscriptionalregulators.CARM1actsasacoactivatorforthemyogenictranscriptionfactorMef2c,andisnecessaryfornormalmusclecelldifferentiation.TheestrogenreceptorisanothertranscriptionfactorthatusesCARM1asoneofseveralcoactivators,actingsynergisticallywithCBPthroughtheGrip1memberofthep160familyofcoactivators.Theinteractionofestrogenreceptorwithvariousligand-dependentcoactivatorsmayproducethetissueselectiveresponseofsomeestrogenreceptorligandsliketamoxifen.

Contributor:KosiGramatikoff,PhD

REFERENCES:BauerUM,DaujatS,NielsenSJ,NightingaleK,KouzaridesT.Methylationatarginine17ofhistoneH3islinkedtogeneactivation.EMBORep.2002Jan;3(1):39-44.ChenSL,LofflerKA,ChenD,StallcupMR,MuscatGE.Thecoactivator-associatedargininemethyltransferaseisnecessaryformuscledifferentiation:CARM1coactivatesmyocyteenhancerfactor-2.JBiolChem.2002Feb8;277(6):4324-33.Chen,D.etal.(1999)Regulationoftranscriptionbyaproteinmethyltransferase.Science284(5423),2174-7KohSS,LiH,LeeYH,WidelitzRB,ChuongCM,StallcupMR.Synergisticcoactivatorfunctionbycoactivator-associatedargininemethyltransferase(CARM)1andbeta-cateninwithtwodifferentclassesofDNA-bindingtranscriptionalactivators.JBiolChem.2002Jul19;277(29):26031-5.Ma,H.etal.(2001)Hormone-dependent,CARM1-directed,arginine-specificmethylationofhistoneH3onasteroid-regulatedpromoter.Curr.Biol.11(24),1981-5McDonnellDP,NorrisJD.Connectionsandregulationofthehumanestrogenreceptor.Science.2002May31;296(5573):1642-4.Review.Xu,W.etal.(2001)Atranscriptionalswitchmediatedbycofactormethylation.Science294(5551),2507-11